Application of MEMS in Drug Delivery 153
Figure 7.2. The temporal modulation of the cellularity present in the various stages of the
inﬂammatory and wound healing response. The intensity and time variables are dependent
upon the extent of the injury created by implantation and the size, shape, topography, and
chemical/physical properties of the device.
leukocytes (PMN), monocytes, and lymphocytes (Fig. 7.2). These inﬂammatory
cells actively migrate from the vasculature in response to chemotactic factors
present at the implant site. Protein-rich ﬂuid (exudate) accompanies this cellular
movement. Further, increased vascular permeability facilitates this movement
resulting in accumulation of cells and exudate, and it is the result of several mech-
anisms including endothelial contraction, cytoskeletal reorganization, leukocyte-
mediated endothelial cell injury and leakage from regenerated capillaries.
with the device itself, the extent of tissue injury proportionally contributes to the
overall extent of the inﬂammatory response. Placement is also critical, as more
destruction/injury of tissue in general leads to a more active acute inﬂammatory
The predominant cell type within the exudate during the acute phase is the
poly-morphonuclear leukocyte (PMN), also called a neutrophil. Its major role is
to attack and digest (phagocytose) bacteria, tissue debris and the foreign material,
so that wound healing can proceed.
. Although BioMEMS are not generally
phagocytosed by PMNs or macrophages due to the disparity in size, certain events
in phagocytosis are known to occur. While the implant size may prevent its total
ingestion by macrophages, they will attach to the device and undergo what is
termed “frustrated phagocytosis”.
This process does not involve engulfment
of the BioMEMS, but does cause the extracellular release of leukocyte products
(lysosomal enzymes, proteases and free radicals) in an attempt to degrade the
surface contact material (Fig. 7.3).
In general, the number of PMNs throughout
the implantation time is indicative of negative compatibility or even toxic effect
induced by the device leading to unsatisfactory overall biocompatibility.
stable large PMN population over extended periods of time suggests a continued
cellular migration from the vascular system since the lifetime of the PMN is
relatively short (48 hours) leading to an unresolved inﬂammatory phase, a sign
of poor biocompatibility of the BioMEMS.
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